This invention relates to novel platinum-polymer conjugates, to pharmaceutical compositions comprising them, and to their use as antitumor agents in humans and animals.
It is known that cisplatin, i.e., cis-[Pt(NH.sub.3).sub.2 Cl.sub.2 ] is effective against several types of animal tumors and has been used successfully in treating certain types of malignancies in humans. A number of other platinum complexes have been tested for antitumor activity, e.g., increased life span for mice having implanted tumors such as L-1210 lymphoid leukemia.
An oligomeric, platinum complex is disclosed in Yolles U.S. Pat. No. 4,283,342. These complexes contain bridging halogen ligands as well as a number of platinum ions in both therapeutic and non-therapeutic forms in the complex. Three bis-platinum complexes were reported by Rochon et al., J. Clin. Hematology & Oncology, 12, 39-43 (May, 1982). Two of those showed no activity against L-1210 lymphoid leukemia, while a third showed a low level of activity but also showed significant toxicity.
Andrulis and Schwartz, U.S. Pat. No. 4,680,308, claims 1,2-diaminocyclohexane complexes having substantial stability in water solutions.
Andrulis and Schwartz, U.S. Pat. No. 4,565,884, claims diamino bis-platinum complex having water solubility, antitumor activity and low toxicity. U.S. application Ser. No. 819,967, filed Jan. 21, 1986, now U.S. Pat. No. 4,720,504, claims the use thereof as antitumor agents.
Gale et al., U.S. Pat. No. 4,137,248, and Kidani et al., U.S. Pat. No. 4,169,846, disclose monomeric complexes of [1,2-diaminocyclohexane]Pt(II). Kidani et al., U.S. Pat. No. 4,200,583, discloses platinum(II) complexes of 1,2-diamino-cyclohexane and one or two sugar acid (Dglucuronic acid) moieties. The disclosures of the foregoing patents are incorporated herein by reference.
For Additional Relevant Literature see:
(a) J. Drobnik et al., U.S. Pat. No. 4,659,849, issued Apr. 21, 1987, "Macromolecular Coordination Compound Containing Platinum with Antitumor Activity in Rodents"; PA1 (b) C. E. Carraher et al., J. Polym. Sci. Tech. (Plenum), Vol. 25, 133 (1984); and PA1 (c) H. R. Alcock et al., U.S. Pat. No. 4,151,185 (1979), "Complex or Salt of a Pt(II) Compound and a Nitrogen-Containing Polymer.
A need exists for platinum complexes with lower toxicity and/or which transport higher amounts of Pt to the tumor site, thereby enhancing antitumor activity.